Synthetic absorbable autoclaveable monofilament fibers and brachytherapy seed spacers

ABSTRACT

The present invention is directed to absorbable, autoclaveable, monofilament fibers prepared from absorbable glycolide-rich polymers, in which the fibers are oriented in the total draw ratio range 4.1 to 5.9X, and are annealed at a temperature between about 165° C. and about 185° C; to brachytherapy seed spacers manufactured from the absorbable, autoclaveable, glycolide-rich polymers, monofilament fibers; and to methods of manufacturing such fibers and brachytherapy seed spacers.

FIELD OF THE INVENTION

[0001] The present invention relates to synthetic, absorbable monofilament fibers of glycolide-based polymers, especiallypoly(lactide-co-glycolide) copolymers, that are useful in thefabrication of brachytherapy seed spacers in brachytherapy seed deliverysystems.

BACKGROUND OF THE INVENTION

[0002] Prostatic cancer has been estimated to affect as many as one inthree men. In the U.S. alone, this implies an estimated fifty-millionpatients who are candidates for treatment of prostatic cancer. Priormethods of treatment include surgical intervention, externalradiotherapy, and other brachytherapy (interstitial radiation)techniques. A general discussion of the localized use of radiationtherapy is found in Bagshaw, M. A., Kaplan, I. D. and Cox, R. C.,Radiation Therapy for Localized Disease, CANCER 71: 939-952, 1993.Disadvantages associated with surgical intervention include impotenceand incontinence. External radiotherapy may have deleterious effects onsurrounding normal tissues (e.g., the bladder, the rectum, and theurethra). In contrast, brachytherapy diminishes complications such asimpotence and incontinence, and allows a higher and more concentratedradiation dose to be delivered to the prostate gland as compared toexternal radiotherapy. An additional advantage of brachytherapy is thattreatment can be accomplished within a matter of days as compared toweeks, greatly reducing radiation exposure of the adjacent organs.

[0003] Prostate brachytherapy can be divided into two categories, basedupon the radiation level used. The first category is temporaryimplantation, which uses high activity sources, and the second categoryis permanent implantation, which uses lower activity sources. These twotechniques are described in Porter, A. T. and Forman, J. D., ProstateBrachytherapy, CANCER 71: 953-958, 1993. The predominant radioactivesources used in prostate brachytherapy include iodine-125,palladium-103, gold-198, ytterbium-169, and iridium-192. Prostatebrachytherapy can also be categorized based upon the method by which theradioactive material is introduced into the prostate. For example, anopen or closed procedure can be performed via a suprapubic or a perinealretropubic approach.

[0004] Prostate cancer is a common cancer for men. While there arevarious therapies to treat this condition, one of the more successfulapproaches is to expose the prostate gland to radiation by implantingradioactive seeds. The seeds are implanted in rows and are carefullyspaced to match the specific geometry of the patient's prostate glandand to assure adequate radiation dosages to the tissue. Currenttechniques to implant these seeds include loading them one at a timeinto the cannula of a needle-like insertion device, which may bereferred to as a brachytherapy needle. Between each seed may be placed aspacer. In this procedure, a separate brachytherapy needle is loaded foreach row of seeds to be implanted.

[0005] Although seed spacers may be made from a variety of materials,both absorbable and non-absorbable, there are advantages if the materialis absorbable. These advantages include minimizing or eliminating anyeffects due to the long-term presence of the material in the body.Absorbable materials include catgut, collagen, and synthetic absorbablepolymers. Catgut and collagen usually degrade by an enzymatic mechanism,as opposed to a chemical mechanism such as reaction with water, that is,hydrolysis. The preferred method of sterilization for brachytherapyseeds and spacers is steam sterilization (autoclaving). When catgut isused as a seed spacer material, the autoclaving process utilized maymake the spacer soft, presumably by the plastisizing effects of thewater which these materials uptake during exposure. Besides notretaining physical characteristics, catgut seed spacers also can changeshape when exposed to autoclaving. Present-day synthetic absorbablematerials do not uptake as much water as catgut or collagen. They do,however, degrade by a hydrolysis mechanism. It is well known that thesehydrolysis reactions occur at faster rates at higher temperatures. Asthe preferred sterilization method for brachytherapy seeds and spacersis steam sterilization (autoclaving), it is surprising that syntheticmaterials known to date can effectively function in these applications.Indeed, based on the knowledge that synthetic absorbable polymersgenerally degrade by chemical hydrolysis, most would not even considerthem for use as medical devices that would be sterilized by autoclaving.

[0006] One approach to minimizing the effects of steam sterilization onthe premature degradation of seed spacers made from synthetic absorbablepolymers would be to consider those synthetic absorbable polymers thatare much more resistant to hydrolysis. Such a material is polylactide.This material has a much higher probability of maintaining mechanicalproperties required for use in brachytherapy seed delivery devices afterit has been exposed to autoclaving, compared to, for instance,polyglycolide. Yet, because polylactide takes so much longer to absorbin the body, it is not generally a material of choice. The high-lactidepolymer, 95/5 poly(lactide-co-glycolide), used in the production ofcertain long-term commercial suture materials useful in certainorthopedic surgical procedures, also takes too long to absorb in thebrachytherapy procedures.

[0007] Other problems exist with certain synthetic absorbable polymers.For instance, the synthetic absorbable polymer poly(p-dioxanone),although known to retain its strength for much longer time periods thanpolyglycolide, is too low melting to be suitable for sterilization byautoclaving. As such, proper selection of material is an importantcriterion in the manufacture of monofilament fibers having propertiessuitable for use as brachytherapy seed spacers.

[0008] In addition to material selection, we have found that the processof manufacture is an important factor. Although injection moldingappears to be an entirely suitable manufacturing process to make seedspacers, if injection molding most synthetic absorbable polymers isutilized as the manufacturing process, the spacers so produced tend tobreak down excessively during the sterilization process, retaining verylittle strength. We have found a process of making brachytherapy seedspacers from glycolide-rich synthetic absorbable polymers entailing apreferred extrusion, drawing, and annealing process to providemonofilament fibers with suitable properties which can be cut to length.

[0009] Monofilament fiber, for use in many applications, needs to beparticularly straight, devoid of curves or bows, to allow properfunctioning. One such application is brachytherapy seed spacers. If theseeds are curved or bowed, they may jam the applier during applicationof the seed/seed spacer assembly. Additionally, undesirable dimensionalspacing variation may result if the seeds are curved initially, or worseyet, curve or bow irreproducibily once in the assembly, as this mayinitially go undetected. Since the function of brachytherapy seedspacers is to help position radioactive seeds to provide radioactivityin spatially suitable pattern, the seeds must be sufficientlydimensionally accurate and stable. Fibers made by some spinningprocesses are not straight after extrusion and drawing. They tend toretain some coil memory. Even after rack annealing, fibers made by someprocesses still can be curved due to residual coil memory.

[0010] Other various process conditions may adversely affect theproperties required of the fibers for use as brachytherapy seed spacers.Upon sterilization by autoclaving, too much undesirable shrinkage inlength may occur or the parts may undergo warping or bending.

[0011] Besides the “brooming” that may be experienced upon cuttingfibers to length, some fabricated devices, i.e. seed spacers, also may“broom” or split during surgery under mechanical loading. Too muchundesirable shrinkage in length, warping or bending upon autoclavingsterilization, or “brooming” or collapse during loading are failuresthat are particularly troublesome, as they occur at a point when theyare difficult to detect or worse yet, during the actual surgicalprocedure.

[0012] It would be advantageous to develop a synthetic, absorbablemonofilament fiber that both is absorbable by the body and maintainsmechanical properties such that the fibers are suitable for use asbrachytherapy seed spacers in brachytherapy seed delivery systems. Italso would be advantageous to provide robust processes for reliablymaking such synthetic absorbable monofilament fibers havingabsorbability and mechanical strength suitable for use as brachytherapyseed spacers.

[0013] According to the present invention, a manufacturing process isprovided for the production of a synthetic, absorbable, monofilamentfiber suitable for the fabrication of medical devices that requireautoclaving as the means of sterilization, such as seed spacers. We havediscovered unexpectedly that monofilament fibers prepared from certainglycolide-rich copolymers, which fibers have been oriented in a totaldraw ratio of 4.1 to 5.9X, and have been annealed between about 165° C.and 185° C., can undergo a sterilizing autoclave cycle and still retainsufficient properties so as to allow their use in certain medicalprocedures, including brachytherapy.

SUMMARY OF THE INVENTION

[0014] The present invention is directed towards monofilament fibersprepared from polymers containing about 80 to 100 mole percent,preferably about 85 to 100 mole percent, polymerized glycolide monomer.The glycolide homopolymer also is known as polyglycolide or aspolyglycolic acid. Preferably the fibers are prepared from polymerscomprising 0 to about 15 mole percent polymerized lactide monomer and100 to about 85 mole percent polymerized glycolide monomer, i.e.poly(lactide-co-glycolide). Most preferably, the polymers comprise about10 mole percent polymerized lactide monomer and about 90 mole percentpolymerized glycolide monomer. The fibers are oriented at a total drawratio range of 4.1 to 5.9X, and are annealed at a temperature betweenabout 165° C. and about 185° C. Such fibers are absorbable by the bodyand are capable of undergoing an autoclave process used to sterilizebrachytherapy seed spacers, while retaining mechanical propertiesrequired for use as brachytherapy seed spacers in brachytherapy seeddelivery devices. The invention also is directed to brachytherapy seedspacers prepared from the monofilament fibers. The invention also isdirected to methods of manufacturing such fibers and brachytherapy seedspacers.

DETAILED DESCRIPTION OF THE INVENTION

[0015] Polymers used in preparation of the monofilament fibers of thepresent invention must be absorbable by the body when used asbrachytherapy seed spacers. By absorbable, it is meant that the materialdoes not simply dissolve away from the implant site, but is converted tolower molecular weight species that are removed from the site andusually from the body by biological means. The conversion to lowermolecular weight species, in the case of most synthetic absorbablepolymers, is effected by chain cleavage by chemical hydrolysis. In thecase of brachytherapy seed spacers, it is preferable to have the devices“cleared” in no more than about three or four months after theprocedure.

[0016] In addition to being absorbable, the fibers prepared from thepolymers must possess certain mechanical properties in order to beuseful as brachytherapy seed spacers. In particular, the column strengthof the fiber, at a minimum, must be effective to prevent the fiber fromsplitting or brooming upon cutting to length in the manufacture of seedspacers. Preferably, the column strength of the fiber, and subsequentlythe seed spacer, will be at least 3.5 pounds after autoclaving. Thesurface of the fiber must be sufficiently smooth for use asbrachytherapy seed spacers. In addition, the fiber must be dimensionallystable and autoclaveable, meaning that the fiber retains shape anddimension effective for use as a seed spacer when subjected to anautoclaving process suitable for sterilization of seed spacers andpracticed in the hospital environment.

[0017] As mentioned earlier, polylactide homopolymers have been found toprovide adequate mechanical properties, but are deficient in that theytake too long to be absorbed by the body. The melting temperature ofpoly(p-dioxanone) polymer is too low to survive the autoclave process.The synthetic absorbable polymers containing polymerized glycolide thathave glass transition temperatures below room temperature and that havefound commercial utility as monofilament sutures, such as the segmentedcopolymers of glycolide and caprolactone, generally do not have themechanical properties needed to function as seed spacers after beingsterilized by autoclaving. We have thus found that not all syntheticabsorbable polymers function equally as seed spacer materials.

[0018] It has been unexpectedly discovered that monofilament fibersprepared from glycolide-rich polymers containing about 85 to 100 molepercent polymerized glycolide, preferably made frompoly(lactide-co-glycolide), comprising from 0/100 to about 15/85 molepercent lactide-glycolide, and most preferably, 10/90poly(lactide-co-glycolide), in which the fibers have been oriented inthe total draw ratio range of 4.1 to 5.9X and in which the fibers havebeen annealed at a temperature between about 165° to about 185° C., maybe used to reliably fabricate absorbable, autoclaveable brachytherapyseed spacers for use in brachytherapy seed delivery devices. Despitebeing absorbable in the body by virtue of a relatively facile reactionrate with water; that is, relatively facile chemical hydrolysis, seedspacers of the subject invention can withstand exposure to water (steam)at the high temperatures, and for the time periods necessary tosterilize by a conventional autoclaving cycle.

[0019] Polymers used to prepare fibers according to the presentinvention generally are prepared from 100 to about 80 mole percentglycolide monomer and from 0 to about 20 mole percent of acopolymerizable comonomer. Exemplary comonomers may be selected from thegroup consisting of L(−)-lactide, D(+)-lactide, meso-lactide,p-dioxanone, trimethylene carbonate and epsilon-caprolactone. If lessthan about 80 mole percent glycolide is used, the fibers manufacturedtherefrom will not possess sufficient mechanical properties required foruse in brachytherapy seed spacers. A preferred comonomer is lactide,especially at about a 10 mole percent level. Other sequences may beincorporated in the polymer, for instance, by adding analpha,omega-dihydroxy compound at the start of the polymerization.

[0020] Generally, the polymers of the present invention have molecularweights, prior to extrusion, corresponding to inherent viscosity (IV)values of about 1.0 to about 2.5 dL/g, as measured inhexafluroisopropanol (HFIP) at 25° C., at a concentration of 0.1 g/dL.It is preferable that the IV values of the resins range from 1.2 to 2.1dL/g, more preferably between 1.3 and 2.0 dL/g, and most preferablybetween 1.4 and 1.7 dL/g. It should be understood that if the molecularweight of the polymer were too low, it would be very difficult to orientthe fiber in the draw ratio range required according to the presentinvention. If the molecular weight is too high, difficulty in conveyingthe molten resin during extrusion may result.

[0021] In a process for making monofilament fibers disclosed in U.S.Pat. No. 4,671,280, entitled Surgical Fastening Device And Method forManufacture, in the name of Dorband et al., the contents of which arehereby incorporated by reference in their entirety, the fibers preparedfrom polymers comprising greater than 80 mole percent polymerizedglycolide are oriented in a total draw ratio of 7.4 X and annealed at135° C. On the other hand, fibers according to the present inventionmust be oriented in a total draw ratio of 4.1 to 5.9X, more preferablyfrom about 4.5 to about 5.5. When the total draw ratio is too low, thefibers exhibit insufficient column strength retention after autoclavingwhen used as a brachytherapy seed spacer. When the total draw ratio istoo high, the surface of the resulting fiber may be too rough for use asa seed spacer, and/or the ends of the fibers may easily split apart, or“broom”, upon cutting to length or during mechanical loading as occursduring introduction of a seed/seed spacer assembly in surgery.

[0022] In order for the process used to manufacture fibers according tothe present invention to be robust, it should consistently provide fiberhaving the mechanical properties required for use in brachytherapy seedspacers, particularly dimensional stability and surface smoothness. Wesurprisingly have discovered that when the extruded, orientedmonofilament fibers comprising 100 to about 80 mole percent polymerizedglycolide are oriented to a total draw ratio between 4.1 to 5.9X andannealed at a temperature between about 165° C. and about 185° C.,fibers that exhibit required dimensional stability and surfacesmoothness consistently are provided. When the annealing temperature isless than about 165° C., e.g. about 155° C., the fibers often exhibitinsufficient mechanical properties such as bowing. More preferably, thefibers are annealed between about 170° C. and about 180° C. Even morepreferably, the fibers are annealed at about 175° C.

[0023] Upon sterilization by autoclaving, too much undesirable shrinkagein length may occur, or parts may undergo warping or bending. Besidesthe “brooming” that may be experienced upon cutting fibers to length,some fabricated devices, i.e. seed spacers, also may “broom” or splitduring surgery under mechanical loading. Fibers and spacers that exhibittoo much undesirable shrinkage in length, warping or bending uponautoclaving sterilization, or “brooming”, or collapse during loading areconsidered ineffective for use in brachtherapy.

[0024] By “autoclaveable”, it is meant that the fiber, in the form of aseed spacer, maintains at least 3.5 lbs of column strength and does notwarp or bend during the autoclave cycle, thus preventing its use as abrachytherapy seed spacer.

[0025] Although seed spacer diameters between about 30 and 40 mils areparticularly advantageous, it is to be understood that the diameter ofmonofilament fibers of the subject invention can be as low as about 20mils and as high as about 60 mils or greater. Generally thecross-section of the fibers will be circular, but other shapes may beused to advantage. In the case of non-circular cross-sections,corresponding cross-sectional areas will dominate.

[0026] Processes for making the glycolide-rich fibers and brachytherapyseed spacers of the present invention are set forth herein.

Example 1

[0027] Polymers and Polymerization:

[0028] Generally the polymers of the present invention have molecularweights, prior to extrusion, corresponding to inherent viscosity (IV)values of about 1.0 to about 2.5 dL/g, as measured inhexafluroisopropanol (HFIP) at 25° C. at a concentration of 0.1 g/dL. Itis preferable that the IV values of the resins range from 1.2 to 2. 1,more preferably between 1.3 and 2.0, and most preferably between 1.4 and1.7 dL/g. Preferably the polymer is 10/90 molar ratiopoly(lactide-co-glycolide). In those cases in which the polymerizedglycolide content is very high, for instance 97 to 100 mole percent, theresins may be very difficult to dissolve, even in HFIP, if they havebeen allowed to crystallize significantly. Inherent viscositymeasurements may then need to be made after first melting a sample ofthe (dried) resin and then quickly quenching it to avoidcrystallization. Samples, so treated, usually can be dissolved in HFIPof IV determinations.

[0029] The polymers of the present invention generally can be made bythe ring opening polymerization of the glycolide monomer, and in thecase of certain copolymers, monomers selected from the group consistingof L(−)-lactide, D(+)-lactide, meso-lactide, p-dioxanone, trimethylenecarbonate and epsilon-caprolactone. These other monomers may be used inany combination with glycolide monomer, provided that the formed polymerresin suitable for extrusion contains at least 80 mole percentglycolide. The polymerizations can be conducted, by placing the monomeror monomers, a catalyst such as stannous octoate, and an initiator suchas dodecanol, in a suitable reaction vessel, purging to provide an inertatmosphere, and heating at a sufficient temperature and time. Theresulting polymer can be ground or pelletized to produce resin suitablefor “drying”, that is, the removal of unreacted monomers. Othersequences may be incorporated in the polymer for instance, by adding analpha,omega-dihydroxy compound at the start of the polymerization. Thefinal resin should contain at least 85 mole percent glycolide sequences.

[0030] Extrusion/Orientation:

[0031] Monofilament fibers of the present invention were extruded usinga one-inch horizontal extruder, with water quench temperatures rangingfrom 20° C. to 40° C. (See Table 1). Typical extruder temperaturesranged from 225° C. to 250° C. although depending on the resin,temperatures may range from about 200° C. to about 265° C. The diameterof the extruder die was changed dependent on the amount of orientationprovided to the filament in the next stage. In the experimentsdescribed, die diameters ranged from 200 to 220 mils. The higher thedraw ratio employed, the larger the die diameter was selected so as tohelp keep the oriented fiber diameter fairly constant. By way ofexample, for a final oriented fiber diameter of 35 mils, suitable diediameters may be as low as 140 mils to as high as about 255 mils.

[0032] The filament was oriented in stages between godets with in-lineovens located between the godets. The draw ratio between the first andsecond set of godet rolls is between 4.5 and 5.0X, with oven temperaturebetween 50° C. and 75° C. The third stage has an additional draw ofbetween 1.01 to 1.2, with oven temperatures between 50° C. and 75° C.TABLE 1 Godet Oven Godet Oven Godet Elong Quench 1 1 2 2 3 Fiber At TempHeight Speed/Temp Temp Speed Temp Speed Diameter Tensile Break (° C.)(in.) (Fpm/° F.) (° C.) (Fpm) (° C.) (Fpm) (Mils) (Lbs) (%) 20 0.2520    — — — — 29.6 7.3 — 20 0.25 20/127 RT 30 NA NA 29.8 11.1 209 200.25 20/145 RT 66 NA NA 28.3 37.7 88.8 20 0.25 20/125 RT 68 NA NA 27.829.7 54.5 20 0.25 20/137 RT 100 NA NA 28.7 20.4 32.5 20 0.5 20/150 RT120 NA NA 29.8 21.1 10.7 20 0.5 20/147 RT 100 NA NA 32.9 44.8 33.3 200.5 20/145 RT 100 NA NA 34.7 41.4 31.2 20 0.5 20/148 RT 120 NA NA 31.928.4 23.3 20 3.5 20/131 160 100 NA NA 36.2 90.7 50.1 20 2.5 20/131 160100 NA NA 37.1 89.9 51.2 20 3.5 20/131 165 100 NA NA 37.0 91.8 53.2 201.0 20/131 160 100 NA NA 35.8 56.7 36.7 20 5.0 20/131 160 100 NA NA 36.789.0 52.7 20 3.5 20/131 165 100 170 110 35.3 89.1 44.0 20 3.5 15/RT  16555 165 75 36.6 105.9 44.0 40 3.5 15/RT  165 55 165 75 35.5 111.1 41.3 402.0 15/RT  165 55 165 75 35.5 109.5 40.7 40 5.0 15/RT  165 55 165 7536.2 109.0 42.4 40 3.5 15/RT  165 55 165 75 36.4 105.4 42.2 40 3.515/RT  165 55 165 75 36.0 100.6 44.1 40 3.5 15/RT  180 55 180 75 36.280.8 53.5 40 3.5 15/RT  165 55 165 75 35.8 98.6 43.5

[0033] Draw ratios between godets can be calculated by dividing thelinear speed of the later godet by that of the earlier godet, providedthere is no significant slippage of the fiber on the godet rolls. Thatis, with godets 1, 2, and 3 running at 15, 55, 75 feet per minute,respectively, the draw ratio between godets 1 and 2 is 55/15 or 3.67X,between godets 2 and 3 is 75/55 or 1.36. The total draw ratio may becalculated by multiplying the respective individual draw ratios, e.g.3.67×1.36=5.0 for the above example. If there is slippage on the godetrolls, fiber speeds will be used to calculate draw ratio. In the case afiber with a circular cross-section, draw ratios can also be calculatedfrom diameter measurements of the fiber before and after a particulardrawing stage: the square root of the ratio of initial diameter to thatof the final diameter is the draw ratio. In general, for fibers withcircular or non-circular cross-sections, the ratio of the initialcross-sectional area to that of the final cross-sectional area is thedraw ratio.

[0034] Annealing:

[0035] Once the extruded monofilament fiber is oriented, it may bestored on a spool. It is then wound onto a standard rack with minimumtension, for instance approximately one pound. Racks approximately 36inches in length are suitable. The filament tension is controlled duringwinding of the fiber around the rack, such that there may be about 5%change in length after annealing. The wound fiber is placed in the ovenand the oven is purged with nitrogen. While the annealing oven may beheated at a rate of about 1° C. per minute, other heating rates may beused. Alternately, the annealing cycle may include incremental holdtimes at elevated temperatures prior to reaching the final temperaturebetween about 165° C. and 185° C. For instance, an incremental hold timeof 1 hour at 75° C. can be used prior to heating to the finaltemperature. After the heat cycle, the material is cooled to ambienttemperature, manually cut off the rack into 30-inch strands and storedin a vacuum chamber until it is ready to be cut into the finaldimensions.

[0036] Column strength tests were performed on fibers in the followingmanner: The test equipment was set up to have a compression type loadcell of at least 100 lbs. A stainless steel tube that has an insidediameter that accommodates a stylet and needle is used to compress thecut fiber (spacer). The tube is clamped vertically such that the needlepushes the spacer in a downward position. Once the position is set forthe equipment, the gauge length is “zeroed” to ensure that the styletand pusher is not overrun. The crosshead speed is set at 0.5inch/second. The maximum load and displacement at maximum load arerecorded.

[0037] The fibers described in Table 2 were annealed at 145° C. prior toautoclaving and then evaluated for column strength after autoclaving asset forth above. Some of the samples exhibited unacceptable columnstrength after annealing or unacceptably rough surface. TABLE 2 GodetGodet 2 Oven Godet Oven Godet 1 Speed/ 1 3 2 4 Total Sample Speed TempTemp Speed Temp Speed Draw Column Strength ID (fpm) (fpm/° C.) (° C.)(fpm) (° C.) (fpm) Ratio Performance INDM 20.0 NA NA NA NA NA 1.0Disintegrated during XX1-1 autoclaving INDM 20.0 20/42 NA 30 NA NA 1.5Disintegrated during XX2-2 autoclaving INDM 20.0 20/42 NA 68 NA NA 3.4Disintegrated during XX3-1 autoclaving INDM 14.76 20/50 50 62.4 50 72.54.8 Good - meets CS XX11-13 requirements INDM 20.0 20/47 NA 100 NA NA5.0 Good - CS after XX4-1 Autoclaving = 16.16 lbs INDM 20.0 20/55 5498.4 NA 100 5.0 Good - CS after XX7-1 Autoclaving = 20.39 lbs INDM 20.020/55 65 98 NA 100 5.0 Good - CS after XX7-5 Autoclaving = 19.27 lbsINDM 20.0 20/52 72 108 NA 110 5.5 Good - CS after XX8-5 Autoclaving=28.99 lbs INDM 20.0 20/53 NA 120 NA NA 6.0 Not Tested Because XX6-5Unacceptably Rough Surface

[0038] Annealed strands were evaluated against performance criteria suchas straightness, the ability to be cut easily without splitting orbrooming and column strength after autoclaving. Results are presented inTable 3. It is noted that fibers annealed at about 155° C. or lessexhibited inconsistent performance results. Sample 2 a, annealed at 145°C., failed because it did not meet the straightness criterion, i.e. itexhibited bowing. Samples C, D, and G in Table 3, annealed at 155° C.,also failed because they did not meet the straightness criterion. TABLE3 Oven Preheat Duration Set Duration Performance Temp Time Temp Time CSBefore CS After Sample (° C.) (hrs) (° C.) (hrs) StraightnessAutoclaving Autoclaving 1 75 1 145 6 Good Good Good 2 — — 145 6 GoodGood Good   2a — — 145 6 Failed - CS not determined because Bowed samplefailed “Straightness” 3 75 1 155 6 Good Good Good 4 — — 155 6 Good GoodGood A — — 155 6 Good 13.86 12.24 B — — 155 6 Slight Bow 17.17 15.83Fair C — — 155 6 Failed - CS not determined because Bowed sample failed“Straightness” D — — 155 6 Failed - CS not determined because Bowedsample failed “Straightness” G — — 155 6 Failed - CS not determinedbecause Bowed sample failed “Straightness” E — — 175 6 Good 22.93 21.89F — — 175 6 Good 20.36 18.23

[0039] We have unexpectedly discovered that monofilament fibers preparedfrom glycolide-rich polymers described herein above and that have beenoriented in a total draw ratio of 4.1 to 5.9X and that have beenannealed at a temperature between about 165° to about 185° C., may beused to reliably fabricate absorbable, autoclaveable brachytherapy seedspacers for use in brachytherapy seed delivery devices. Utilizing thefibers described above, brachytherapy seed spacers were prepared asfollows:

[0040] Cutting:

[0041] Fibers of the present invention may be cut in any manner thatwill provide the dimensional requirements required for use asbrachytherapy seed spacers. This may include mechanical or thermalmeans. An in-line cutting mechanism provides an economicallyadvantageous way of cutting. Cutting must be conducted so that it doesnot “mushroom”, crush, broom, or delaminate the fiber. Manual cutting ispossible and may be accomplished with a “razor blade” or a “papercutter” type of cutting mechanism. After cutting, the fibers preferablyare stored in a water-free environment, such as a “nitrogen box” or avacuum chamber. Simple cutting mechanisms provide the advantage ofcapital cost avoidance regarding complex equipment. The fibers of thesubject invention have additional advantage in that they can be cut bysimply means without “mushrooming”, crushing, brooming, or delaminating,to allow their use as brachytherapy seed spacers.

[0042] Sterilization by Autoclaving:

[0043] Different types of commercial autoclaving sterilizers areavailable. Two major classes are known by some as the “pre-vacuum” typeand the “gravity-displacement” type. The pre-vacuum type of sterilizerdepends upon one or more pressure and vacuum excursions at the beginningof the cycle to remove air. This method of operation results in shortercycle times for wrapped items because of the rapid removal of air fromthe chamber (and the “load” or items to be sterilized) by a vacuumsystem and because of a usually higher operating temperature (forinstance 132° C. to 135° C., or 250° F. to 254° F.). Typical operatingparameters for a pre-vacuum type of sterilizer are 3 to 4 minutes at132° C. to 135° C. A gravity-displacement type of sterilizer is one inwhich incoming steam displaces residual air through a port or drain inor near the bottom of the sterilizer chamber. Typical operatingparameters for a gravity-displacement type of sterilizer include 15 to30 minutes at 121 to 123° C.

[0044] Four types of sterilization cycles were used to sterilize thesamples: (1) pre-vacuum at 275° F. (135° C.) for 10 minutes; (2)gravity-displacement at 275° F. (135° C.) for 15 minutes; (3)gravity-displacement at 275° F. (1 35° C.) for 25 minutes; (4)gravity-displacement at 254° F. (123.3° C.) for 30 minutes.

Example 2

[0045] Another method of manufacturing a dimensionally stable absorbablespacer according to the present invention includes the following steps.Using a typical horizontal extruder, such as a one-inch 24:1 extruder,pellets of the polymer are melted and then extruded through a die toform mono filaments. The filaments then are quenched, for instance,using a heated water bath. More particularly, the horizontal extruderincludes a number of zones, for instance, three zones, all which may beset independently at temperatures of between about 200° C. and about260° C., and preferably between about 225° C. and 250° C. As the polymerpellets are passed through the three zones, they melt and the meltedpolymer is forced through a flange which is heated to a temperature ofbetween about 210° C. and 265° C. and preferably between about 230° C.and 255° C. After passing through the heated flange, the melted polymerenters a pump, which has a temperature of between about 210° C. and 265°C. and preferably between about 232° C. and 255° C. Finally, the meltedpolymer is forced through a die having a predetermined diameter of, forexample 0.22 inch. The polymer then forms a long rod, which is suspendedin air for approximately 2 to 4 inches and quenched in a tank of waterhaving a temperature of approximately 30° C. to 40° C., thus completingthe extrusion process. Immediately following extrusion, or alternatelyafter some time has passed, the filaments may be oriented to about 5:1draw ratio by stretching them between heated godet rolls or bystretching them between (optionally heated) godet rolls providing(additional) heating means such as can be achieved with in-line ovens.It is clear to those familiar with fiber manufacture that differentmeans of stretching a fiber to achieve a particular draw ratio areavailable. In particular, the extruded rod may be oriented by winding itaround a first roller, which is turning at a rate of approximately 4 to6 meters per minute, which pulls the extruded rod out of the bath. Theextruded rod may then be wound around a second roll that turns at a rateof 4 to 6 meters per minute. After passing around the second roll, theextruded rod may be passed through a first oven that is set at atemperature of approximately 50° C. to 55° C. After passing through thefirst oven, the extruded rod may be passed around a third roll that isturning at a rate of between 17 and 21 meters per minute. After passingaround the third roll, the extruded rod is passed through a second oventhat is set at a temperature of between 50° C. to 55° C. After passingthrough the second oven, the extruded rod is wound around a fourth rollthat is turning at a rate of between 24 and 31.5 meters per minute.Prior to cutting and sterilizing, the rod must be annealed between about165° C. and 185° C.

[0046] It will be recognized that an absorbable, dimensionally stable,autoclaveable seed spacer according to the present invention may bemodified to include certain types of medication which may be absorbed asthe spacer is absorbed. Such medications might include, for example,anti-inflammatory, anti-cancer or certain sustained-release drugs. Aseed spacer according to the present invention further may includemarkers or other materials adapted to make the spacer visible toultrasound or x-ray.

[0047] While preferred embodiments of the present invention have beenshown and described herein, it will be obvious to those skilled in theart that such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. Accordingly, it isintended that the invention be limited only by the spirit and scope ofthe appended claims.

We claim:
 1. A process for the manufacture of a monofilament fiber,comprising the steps of: extruding a polymer comprising 100 to about 80mole percent polymerized glycolide to form a monofilament fiber,orienting the extruded monofilament fiber to a total draw ratio of 4.1to 5.9X; and annealing the oriented monofilament fiber at a temperatureof about 165° to about 185° C.
 2. The process of claim 1 wherein thepolymer comprises up to about 20 mole percent polymerized monomerselected from the group consisting of L(−)-lactide, D(+)-lactide,meso-lactide, p-dioxanone, trimethylene carbonate andepsilon-caprolactone.
 3. The process of claim 2 wherein the polymercomprises about 10 mole percent polymerized lactide and about 90 molepercent polymerized glycolide.
 4. The process of claim 1 wherein thetotal draw ratio is about 4.5 to about 5.5X.
 5. The process of claim 1wherein the monofilament fiber is annealed at a temperature of about170° C. to about 180° C.
 6. The process of claim 4 wherein themonofilament fiber is annealed at a temperature of about 170° C. toabout 180° C.
 7. An absorbable, autoclaveable, monofilament fiberprepared by the process of: extruding a polymer comprising 100 to about80 mole percent polymerized glycolide to form a monofilament fiber,orienting the extruded monofilament fiber to a total draw ratio of 4.1to 5.9X; and annealing the oriented monofilament fiber at a temperaturefrom about 165°to about 185° C.
 8. The fiber of claim 7 wherein thepolymer comprises up to about 20 mole percent polymerized monomerselected from the group consisting of L(−)-lactide, D(+)-lactide,meso-lactide, p-dioxanone, trimethylene carbonate andepsilon-caprolactone.
 9. The fiber of claim 8 wherein the polymercomprises about 10 mole percent polymerized lactide and about 90 molepercent polymerized glycolide.
 10. The fiber of claim 7 wherein thetotal draw ratio is about 4.5 to about 5.5X.
 11. The fiber of claim 7wherein the monofilament fiber is annealed at a temperature from about170° C. to about 1 80° C.
 12. The fiber of claim 10 wherein themonofilament fiber is annealed at a temperature of about 170° C. toabout 180° C.
 13. A brachytherapy seed spacer comprising an absorbable,autoclaveable monofilament fiber prepared by the process of: extruding apolymer comprising 100 to about 80 mole percent polymerized glycolide toform a monofilament fiber, orienting the extruded monofilament fiber toa total draw ratio of 4.1 to 5.9X; and annealing the orientedmonofilament fiber at a temperature of about 165° to about 185° C. 14.The seed spacer of claim 13 wherein the polymer comprises up to about 20mole percent polymerized monomer selected from the group consisting ofL(−)-lactide, D(+)-lactide, meso-lactide, p-dioxanone, trimethylenecarbonate and epsilon-caprolactone.
 15. The seed spacer of claim 14wherein the polymer comprises about 10 mole percent polymerized lactideand about 90 mole percent polymerized glycolide.
 16. The seed spacer ofclaim 13 wherein the total draw ratio is about 4.5 to about 5.5X. 17.The seed spacer of claim 13 wherein the monofilament fiber is annealedat a temperature from about 170° C. to about 180° C.
 18. The seed spacerof claim 16 wherein the monofilament fiber is annealed at a temperaturefrom about 170° C. to about 180° C.
 19. A process for the manufacture ofa brachytherapy seed spacer, comprising the steps of: extruding apolymer comprising 100 to about 80 mole percent polymerized glycolide toprepare a mono filament fiber, orienting the extruded monofilament fiberto a total draw ratio of 4.1 to 5.9X, annealing the orientedmonofilament fiber at a temperature from about 165° to about 185° C; andcutting the annealed, oriented monofilament fiber to a pre-determineddimension effective for use as the brachytherapy seed spacer.
 20. Theprocess of claim 19 wherein the polymer comprises up to about 20 molepercent polymerized monomer selected from the group consisting ofL(−)-lactide, D(+)-lactide, meso-lactide, p-dioxanone, trimethylenecarbonate and epsilon-caprolactone.
 21. The process of claim 20 whereinthe polymer comprises about 10 mole percent polymerized lactide andabout 90 mole percent polymerized glycolide.
 22. The process of claim 19wherein the total draw ratio is about 4.5 to about 5.5X.
 23. The processof claim 19 wherein the monofilament fiber is annealed at a temperaturefrom about 170° C to about 180° C.
 24. The process of claim 22 whereinthe monofilament fiber is annealed at a temperature from about 170° C toabout 180° C.